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AIM: Blockade of interleukin-6 (IL-6) or its receptor (IL-6R) is effective in preventing the progression of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In the present study, we established a novel cell-based assay for identifying small molecule IL-6R antagonists. METHODS: HEK293A cells were transfected with recombinant plasmids pTaglite-SNAP-IL6R and pABhFc-IL6 to obtain membrane-bound IL-6R and recombinant human IL-6 coupled with human Fc fragment (rhIL-6), respectively. A novel screening assay based on the interaction between IL-6R and rhIL-6 was established, optimized and validated. The stability of the assay was also assessed by calculating the Z'-factor. RESULTS: RhIL-6 dose-dependently bound to IL-6R expressed at HEK293A cell surface. The IC50 value of the known antagonist ab47215 was 0.38±0.08 µg/mL, which was consistent with that obtained using the traditional method (0.36±0.14 µg/mL). The value of Z'-factor was 0.68, suggesting that the novel assay was stable for high throughput screening. A total of 474 compounds were screened using the novel screening assay, and 3 compounds exhibited antagonistic activities (IC50=8.73±0.28, 32.32±9.08, 57.83±4.24 µg/mL). Furthermore, the active compounds dose-dependently inhibited IL-6-induced proliferation of 7TD1 cells, and reduced IL-6-induced STAT3 phosphorylation in U937 cells. CONCLUSION: A novel cell-based screening assay for identifying small molecule IL-6R antagonists was established, which simplifies the procedures in traditional cellular ELISA screening and profiling and reduces the costs.
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Membrana Celular/efectos de los fármacos , Descubrimiento de Drogas/métodos , Ensayos Analíticos de Alto Rendimiento , Mediadores de Inflamación/farmacología , Receptores de Interleucina-6/antagonistas & inhibidores , Unión Competitiva , Membrana Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Células HEK293 , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Ligandos , Fosforilación , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Factor de Transcripción STAT3/metabolismo , Factores de Tiempo , Transfección , Células U937RESUMEN
Organizational resilience is a key concept in the study of sustainable corporate growth and indicates an organization's capacity to recover from adversity. It plays a crucial role in responding to uncertain crises. In recent years, academic interest in organizational resilience has increasingly gained prominence. This research uses CiteSpace and VOSviewer to provide a thorough visual analysis of pertinent international literature based on 342 pieces of closely linked literature about organizational resilience. The findings suggest that organizational resilience research is currently experiencing a development phase. Within this field, there is a substantial number of scholars involved, with the most prolific among them including Aleksic Aleksandar, Prayag Girish, and Griffiths Andrew. The networks of collaboration among these authors, nevertheless, are very scattered. Co-citation network research reveals the academics with the biggest sway in the field. Organizational resilience, conservation of resources theory, crisis management, corporate social responsibility, and emergency management are identified as research hotspots within the keyword co-citation network. Furthermore, to determine which countries and regions are the most influential, this study has created a cooperative network among them. China, the United States, and England are the top three nations with articles published. Not only are the highly cited journals respected in the management sector, but they also showcase noteworthy research accomplishments within the field. The purpose of this study is to investigate potential avenues for future research and offer helpful sources for choosing research subjects and developing theoretical frameworks in this area. The analysis is highly valuable as a reference for research on organizational resilience in different settings in the future.
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Polymeric materials are indispensable in our daily lives. However, the generation of vast amounts of waste polymers poses significant environmental and ecological challenges. Instead of resorting to landfilling or incineration, strategies for polymer recycling offer a promising approach to mitigate environmental pollution. Pioneering studies have demonstrated the alcoholysis of waste polyesters and polycarbonates; however, these processes typically require the use of catalysts. Moreover, the development of strategies for catalyst removal and recycling is crucial, particularly in some industrial applications. In contrast, we present a catalyst-free method for the alcoholysis of common polyester and polycarbonate materials into small organic molecules. Certain polar organic solvents exhibit remarkable efficiency in polymer degradation under catalyst-free conditions. Employing these polar solvents, both polymer resins and commercially available products could be effectively degraded via alcoholysis. Our design contributes a straightforward route for recycling waste polymeric materials.
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An understanding of the excited-state process and the sensing mechanism for specific anions can be helpful for the design and synthesis of fluorescent sensors in analytical chemistry and biotechnology. Here, we theoretically investigated the fluorescent response mechanism of a reported acylhydrazone-based fluorescent sensor (Soft Matter, 2019, 15, 6690) for fluoride recognition using the time-dependent density functional theory approach. At the M06/TZVP/SCM level, the vertical excitation energies, which were calculated based on the ground state and first singlet-state geometries of the sensor molecule, agreed well with the experimental ultraviolet-visible and fluorescence spectra. Therefore, the time-dependent density functional theory method was considered reasonable and effective. According to the frontier orbital analysis and an excited-state potential energy scan, we proposed an excited-state proton transfer mechanism for the sensor-fluorine complex, where the steric hindrance leads to a high potential barrier. The excited-state proton transfer process facilitates sensor molecule deprotonation, alleviates its steric hindrance effect and expands its conjugated system. As a result, the fluorescence emission band of the sensor molecule was red-shifted significantly with the addition of fluoride anion. Based on this fluorescence difference, the sensor could be used for fluoride anion identification. This work provides a strategy to study sensor-analyte interactions in the excited state and offers an approach to tune the fluorescence emission wavelength of sensor molecules in anionic environments.
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Fluoruros , Protones , Teoría Funcional de la Densidad , Colorantes Fluorescentes/química , Fluoruros/análisis , Espectrometría de FluorescenciaRESUMEN
Due to its variety of functions, rhubarb has been used for thousands of years in many countries. It is commonly used after processing. Processing usually affect the chemical profile and the contents of active compounds in herbals, leading to changes of their bioactivities. Here, an approach of metabolite profiling and diagnostic ion filtering strategy with liquid chromatography-quadrupole/time-of-flight mass spectrometry was established for rapid identification of raw and processed pieces of Rheum palmatum L. (RPL). The comprehensive and unbiased information of 30 batches of RPL covering raw and two general processing methods were given by metabolomic profiles. Using molecular feature extraction algorithm, non-targeted compounds were analyzed in minutes. In total, 73 characteristic markers were extracted and identified by diagnostic ion filtering. They have been further analyzed by partial least squares-support vector machine-based pattern recognition. The comprehensive and rapid method for raw and processed pieces of RPL classification shows good sensitivity, specificity and prediction performance.